Exploring Genetic Susceptibility in Peri-Implantitis

Year 2025, Volume: 35 Issue: 4, 336 - 342, 21.10.2025

Rukiye Ziya , Tolga Polat , Özlem Özge Yılmaz , Hatice Selin Güngörmek , Beste Tacal Aslan

https://doi.org/10.17567/currresdentsci.1567726

Abstract

The investigation of genetic factors influencing peri-implant diseases, particularly peri-implantitis (PI), offers insights into the complex interplay between host genetics and inflammatory responses within oral tissues. Numerous genes encoding cytokines, receptors, and regulatory proteins have been scrutinized for their roles in modulating immune responses and tissue homeostasis around dental implants. Notably, polymorphisms in genes encoding interleukins (IL-1, IL-6, IL-17, IL-10), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinases (MMPs) have emerged as potential genetic markers for susceptibility to peri-implant diseases. Additionally, genes involved in bone metabolism, such as osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANK-L), bone morphogenetic proteins (BMPs), and fibroblast growth factors (FGFs), contribute to peri-implant diseases. Polymorphisms in these genes affect bone resorption and regeneration processes, influencing the stability of dental implants. Variations in these genes can either enhance or hinder bone regeneration, impacting the healing process and the long-term success of implants. Moreover, investigations into less-studied genes like cluster of differentiation 14 (CD14), Chemokine Receptor 2 (CXCR2), and Fragment crystallizable gamma receptor (FcγRs) have revealed additional genetic determinants implicated in the pathogenesis of peri-implant diseases. These genes can influence immune cell function and inflammatory signaling pathways, contributing to the body's response to bacterial biofilms and other factors that compromise implant health. The study of these genetic variations provides a deeper understanding of individual susceptibility to PI and may guide personalized treatment strategies, ultimately improving implant success rate.
Keywords: Peri-implantitis, polymorphism, immunity

Keywords

Peri-implantitis , polymorphism , Immunity

Peri-implantitis Gelişiminde Genetik Yatkınlığın İncelenmesi

Abstract

Peri-implant hastalıkları, özellikle peri-implantitis (PI) etkileyen genetik faktörlerin araştırılması, konak genetiği ile oral dokulardaki inflamatuar yanıtlar arasındaki karmaşık etkileşime dair içgörüler sunar. Sitokinleri, reseptörleri ve düzenleyici proteinleri kodlayan çok sayıda gen, dental implantlar etrafındaki bağışıklık yanıtlarını ve doku homeostazını düzenlemedeki rolleri açısından incelenmiştir. Özellikle, interlökinleri (IL-1, IL-6, IL-17, IL-10), tümör nekroz faktörü-alfa'yı (TNF-α) ve matris metalloproteinazları (MMP'ler) kodlayan genlerdeki polimorfizmler, peri-implant hastalıklarına yatkınlık için potansiyel genetik belirteçler olarak ortaya çıkmıştır. Ek olarak, osteoprotegerin (OPG), nükleer faktör kappa-B ligandının reseptör aktivatörü (RANK-L), kemik morfogenetik proteinleri (BMP'ler) ve fibroblast büyüme faktörleri (FGF'ler) gibi kemik metabolizmasında yer alan genler peri-implant hastalıklarına katkıda bulunur. Bu genlerdeki polimorfizmler kemik rezorpsiyonunu ve rejenerasyon süreçlerini etkileyerek diş implantlarının stabilitesini etkiler. Bu genlerdeki varyasyonlar kemik rejenerasyonunu artırabilir veya engelleyebilir, iyileşme sürecini ve implantların uzun vadeli başarısını etkileyebilir. Ayrıca, farklılaşma kümesi 14 (CD14), Kemokin Reseptörü 2 (CXCR2) ve Fragment kristalize edilebilir gama reseptörü (FcγR'ler) gibi daha az çalışılmış genler üzerindeki araştırmalar, peri-implant hastalıklarının patogenezinde rol oynayan ek genetik belirleyicileri ortaya çıkarmıştır. Bu genler, bağışıklık hücresi fonksiyonunu ve inflamatuar sinyal yollarını etkileyerek vücudun bakteriyel biyofilmlere ve implant sağlığını tehlikeye atan diğer faktörlere verdiği tepkiye katkıda bulunabilir. Bu genetik varyasyonların incelenmesi, PI'ye karşı bireysel duyarlılığın daha derin bir şekilde anlaşılmasını sağlar ve kişiselleştirilmiş tedavi stratejilerine rehberlik ederek nihayetinde implant başarı oranlarını iyileştirebilir.
Anahtar Kelimeler: Bağışıklık, peri-implantitis, polimorfizm

Keywords

Bağışıklık , Peri-implantitis , Polimorfizm

References

• 1. Tefera AT, Girma B, Adane A, et al. Oral health-related quality of life and oral hygiene status among special need school students in Amhara region, Ethiopia. Health Qual Life Outcomes. 2023;21(1):26.
• 2. Moussa A, Ibrahim E, Esmat A, Eissa S, Ramzy M. An overview of oral health status, socio-economic and behavioral risk factors, and the pattern of tooth loss in a sample of Egyptian rural population. Bull Natl Res Cent. 2020;44:1-6.
• 3. Bansal A, Ingle NA, Kaur N, Ingle E. Recent advancements in fluoride: a systematic review. J Int Soc Prev Community Dent. 2015;5(5):341-346.
• 4. Huang R, Li M, Gregory RL. Bacterial interactions in dental biofilm. Virulence. 2011;2(5):435-444.
• 5. Eick S. Biofilms. Monogr Oral Sci. 2021;29:1-11.
• 6. de Araujo Munhoz FB, Nogara PRB, da Costa Junior FR, Branco FP, dos Santos MC. Analysis of MMP-3 polymorphism in osseointegrated implant failure. Braz J Oral Sci. 2016;15(4):304-307.
• 7. Lindhe J, Meyle J, Group D of the European Workshop on Periodontology. Peri‐implant diseases: consensus report of the sixth European workshop on periodontology. J Clin Periodontol. 2008;35:282-285.
• 8. Atala MH, Ustaoğlu G, Çetin H. An Evaluation of Success Factors in Dental Implant Treatment. Anatolian Clin J Med Sci. 2019;24(1):26-31.
• 9. Kirch W, ed. Single nucleotide polymorphism (SNP). Dordrecht, Netherlands: Springer; 2008
• 10. Berglundh T, Lindhe J, Ericsson I, Marinello CP, Liljenberg B, Thornsen P. The soft tissue barrier at implants and teeth. Clin Oral Implants Res. 1991;2(2):81-90.
• 11. Manor Y, Oubaid S, Mardinger O, Chaushu G, Nissan J. Characteristics of early versus late implant failure: a retrospective study. J Oral Maxillofac Surg. 2009;67(12):2649-2652.
• 12. Avila-Ortiz G, Gonzalez-Martin O, Couso-Queiruga E, Wang HL. The peri-implant phenotype. J Periodontol. 2020;91(3):283–288.
• 13. Petković-Ćurčin A, Matić S, Vojvodić D, Stamatović N, Todorović T. Cytokines in pathogenesis of peri-implantitis. Vojnosanit Pregl. 2011;68(5):435-440.
• 14. Schminke B, Vom Orde F, Gruber R, Schliephake H, Bürgers R, Miosge N. The pathology of bone tissue during peri-implantitis. J Dent Res. 2015;94(2):354-361.
• 15. Dilsiz A, Zihni M, Yavuz M. Peri-implant diseases. Cumhuriyet Dent J. 2011;11(1):59–65.
• 16. Lafuente-Ibáñez de Mendoza I, Setien-Olarra A, García-De la Fuente AM, Aguirre-Urizar JM, Marichalar-Mendia X. Role of proinflammatory mutations in peri-implantitis: systematic review and meta-analysis. Int J Implant Dent. 2022;8(1):2.
• 17. Robert F, Pelletier J. Exploring the impact of single-nucleotide polymorphisms on translation. Front Genet. 2018;9:419121.
• 18. Özmen S, Atalı PY, Ağralı ÖB, et al. The effects of MMP3 (rs679620) and VDR (rs731236) gene polymorphisms on dental caries: a pilot study. Eur J Dent. Published online July 19, 2024.
• 19. Chen X, Zhao Y. Genetic involvement in dental implant failure: association with polymorphisms of genes modulating inflammatory responses and bone metabolism. J Oral Implantol. 2019;45(4):318-326.
• 20. Andreiotelli M, Koutayas SO, Madianos PN, Strub JR. Relationship between interleukin-1 genotype and peri-implantitis: a literature review. Quintessence Int. 2008;39(4):289-298.
• 21. Turkmen M, Firatli E. The study of genetic predisposition on periodontitis and peri-implantitis. Niger J Clin Pract. 2022;25(11):1799-1804.
• 22. Mohammadi H, Roochi MM, Sadeghi M, et al. Association between Interleukin-1 Polymorphisms and Susceptibility to Dental Peri-Implant Disease: A Meta-Analysis. Pathogens. 2021;10(12):1600.
• 23. Laine ML, Leonhardt Å, Roos-Jansåker AM, et al. IL‐1RN gene polymorphism is associated with peri‐implantitis. Clin Oral Implants Res. 2006;17(4):380-385.
• 24. Fourmousis I, Vlachos M. Genetic risk factors for the development of periimplantitis. Implant Dent. 2019;28(2):103-114.
• 25. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996;87(6):2095–2147.
• 26. Nicklin MJ, Weith A, Duff GW. A physical map of the region encompassing the human interleukin-1α, interleukin-1β, and interleukin-1 receptor antagonist genes. Genomics. 1994;19(2):382-384.
• 27. Jansson H, Hamberg K, De Bruyn Odont H, Odont GB. Clinical consequences of IL‐1 genotype on early implant failures in patients under periodontal maintenance. Clin Implant Dent Relat Res. 2005;7(1):51-59.
• 28. García-Delaney C, Sánchez-Garcés MÁ, Figueiredo R, Sánchez-Torres A, Gay-Escoda C. Clinical significance of interleukin-1 genotype in smoking patients as a predictor of peri-implantitis: A case-control study. Med Oral Patol Oral Cir Bucal. 2015;20(6).
• 29. Meffert RM. Periodontitis vs peri-implantitis: the same disease? the same treatment? Crit Rev Oral Biol Med. 1996;7(3):278-291.
• 30. Özturk ÖH, Tacal AB, Eken BF, et al. Single nucleotide polymorphisms in IL-1A rs1800587, IL-1B rs1143634, and vitamin D receptor rs731236 in stage III grade B/C periodontitis. Balkan J Med Genet. 2023;25(1):51-60.
• 31. Cardoso JM, Ribeiro AC, Palos C, Proença L, Noronha S, Alves RC. Association between IL-1A and IL-1B gene polymorphisms with peri-implantitis in a Portuguese population: a pilot study. PeerJ. 2022;10:e13729.
• 32. Steen EH, Wang X, Balaji S, et al. The role of the anti-inflammatory cytokine interleukin-10 in tissue fibrosis. Adv Wound Care. 2020;9(4):184-198.
• 33. Jamshidy L, Tadakamadla SK, Choubsaz P, et al. Association of IL-10 and TNF-α polymorphisms with dental peri-implant disease risk: a meta-analysis, meta-regression, and trial sequential analysis. Int J Environ Res Public Health. 2021;18(14):7697.
• 34. Saremi L, Shafizadeh M, Esmaeilzadeh E, et al. Assessment of IL-10, IL-1ß and TNF-α gene polymorphisms in patients with peri-implantitis and healthy controls. Mol Biol Rep. 2021;48:2285-2290.
• 35. Taha GI. Involvement of IL-10 gene polymorphism (rs1800896) and IL-10 level in the development of peri-implantitis. Minerva Dent Oral Sci. 2023.
• 36. Li X, Bechara R, Zhao J, McGeachy MJ, Gaffen SL. IL-17 receptor-based signaling and implications for disease. Nat Immunol. 2019;20(12):1594–1602.
• 37. Talib EQ, Taha GI. Involvement of interleukin-17A (IL-17A) gene polymorphism and interleukin-23 (IL-23) level in the development of peri-implantitis. BDJ Open. 2024;10(1):12.
• 38. Petkovic-Curcin A, Zeljic K, Cikota-Aleksic B, et al. Association of Cytokine Gene Polymorphism with Peri-implantitis Risk. Int J Oral Maxillofac Implants. 2017;32(5).
• 39. Agrawal KK, Chand P, Singh SV, et al. Association of interleukin-1, interleukin-6, collagen type I alpha 1, and osteocalcin gene polymorphisms with early crestal bone loss around submerged dental implants: A nested case control study. J Prosthet Dent. 2023;129(3):425-432.
• 40. Górska R, Gregorek H, Kowalski J, et al. Relationship between clinical parameters and cytokine profiles in inflamed gingival tissue and serum samples from patients with chronic periodontitis. J Clin Periodontol. 2003;30(12):1046-1052.
• 41. Zhao B. Intrinsic restriction of TNF-mediated inflammatory osteoclastogenesis and bone resorption. Front Endocrinol (Lausanne). 2020;11:583561.
• 42. Graves DT, Oskoui M, Volejnikova S, et al. Tumor necrosis factor modulates fibroblast apoptosis, PMN recruitment, and osteoclast formation in response to P. gingivalis infection. J Dent Res. 2001;80(10):1875–1879.
• 43. Duarte PM, De Mendonça AC, Máximo MBB, et al. Differential cytokine expressions affect the severity of peri‐implant disease. Clin Oral Implants Res. 2009;20(5):514-520.
• 44. Saremi L, Esmaeili S, Ghaffari ME, et al. Evaluation of matrix metalloproteinase -1,-2,-3,-7, and-13 gene polymorphisms in patients with chronic periodontitis and healthy controls. Clin Oral Investig. 2023;27(12):7417-7423.
• 45. Astolfi CM, Shinohara AL, Da Silva RA, et al. Genetic polymorphisms in the MMP‐1 and MMP‐3 gene may contribute to chronic periodontitis in a Brazilian population. J Clin Periodontol. 2006;33(10):699-703.
• 46. Gul SS, Abdulkareem AA, Sha AM, Rawlinson A. Diagnostic accuracy of oral fluids biomarker profile to determine the current and future status of periodontal and peri-implant diseases. Diagnostics. 2020;10(10):838.
• 47. Luchian I, Goriuc A, Sandu D, Covasa M. The role of matrix metalloproteinases (MMP-8, MMP-9, MMP-13) in periodontal and peri-implant pathological processes. Int J Mol Sci. 2022;23(3):1806.
• 48. Costa-Junior FR, Alvim-Pereira CC, Alvim-Pereira F, et al. Influence of MMP-8 promoter polymorphism in early osseointegrated implant failure. Clin Oral Investig. 2013;17:311-316.
• 49. de Araujo Munhoz FB, Branco FP, Souza RLR, Dos Santos MC. Matrix metalloproteinases gene polymorphism haplotype is a risk factor to implant loss: A case‐control study. Clin Implant Dent Relat Res. 2018;20(6):1003-1008.
• 50. Vidal C, Formosa R, Xuereb-Anastasi A. Functional polymorphisms within the TNFRSF11B (osteoprotegerin) gene increase the risk for low bone mineral density. J Mol Endocrinol. 2011;47(3):327.
• 51. Zhou J, Zhao Y. Osteoprotegerin gene (OPG) polymorphisms associated with peri-implantitis susceptibility in a Chinese Han population. Med Sci Monit. 2016;22:4271.
• 52. Wynne F, Drummond F, O'Sullivan K, et al. Investigation of the genetic influence of the OPG, VDR (Fok1), and COLIA1 Sp1 polymorphisms on BMD in the Irish population. Calcif Tissue Int. 2002;71(1).
• 53. Kadkhodazadeh M, Tabari ZA, Ardakani MR, et al. Analysis of osteoprotegerin (OPG) gene polymorphism in Iranian patients with chronic periodontitis and peri-implantitis: a cross-sectional study. Eur J Oral Implantol. 2012;5(4):381-388.
• 54. Xu M, Zhang C, Han Y, et al. Association between Osteoprotegerin rs2073618 polymorphism and peri-implantitis susceptibility: a meta-analysis. BMC Oral Health. 2022;22(1):598.
• 55. Díaz-Sánchez RM, Yáñez-Vico RM, Fernández-Olavarría A, et al. Current Approaches of Bone Morphogenetic Proteins in Dentistry. J Oral Implantol. 2015;41(3):337–342.
• 56. Urist MR. Bone: formation by autoinduction. Science. 1965;150(3698):893–899.
• 57. Kelly MP, Vaughn OL, Anderson PA. Systematic Review and Meta-Analysis of Recombinant Human Bone Morphogenetic Protein-2 in Localized Alveolar Ridge and Maxillary Sinus Augmentation. J Oral Maxillofac Surg. 2016;74(5):928–939.
• 58. Park SY, Kim KH, Kim S, Lee YM, Seol YJ. BMP-2 gene delivery-based bone regeneration in dentistry. Pharmaceutics. 2019;11(8):393.
• 59. Rotenberg SA, Tatakis DN. Recombinant Human Bone Morphogenetic Protein‐2 for Peri‐Implant Bone Regeneration: A Case Report. J Periodontol. 2011;82(8):1212-1218.
• 60. Coelho RB, Gonçalves Junior R, Villas-Boas RDM, et al. Haplotypes in BMP4 and FGF genes increase the risk of peri-implantitis. Braz Dent J. 2016;27:367-374.
• 61. Lacey DL, Boyle WJ, Simonet WS, et al. Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab. Nat Rev Drug Discov. 2012;11(5):401–419.
• 62. Kadkhodazadeh M, Ebadian AR, Gholami GA, et al. Analysis of RANKL gene polymorphism (rs9533156 and rs2277438) in Iranian patients with chronic periodontitis and periimplantitis. Arch Oral Biol. 2013;58(5):530-536.
• 63. Park OJ, Shin SY, Choi Y, et al. The association of osteoprotegerin gene polymorphisms with periodontitis. Oral Dis. 2008;14(5):440–444.
• 64. Kadkhodazadeh M, Baghani Z, Ebadian AR, et al. Receptor activator of nuclear factor kappa-B gene polymorphisms in Iranian periodontitis and peri-implantitis patients. J Periodontal Implant Sci. 2014;44(3):141.
• 65. Silva RCE, Reis MBL, Arid J, et al. Association between genetic polymorphisms in RANK, RANKL and OPG and peri-implant diseases in patients from the Amazon region. Braz Dent J. 2020;31(1):63-68.
• 66. Ribeiro R, Melo R, Tortamano Neto P, et al. Polymorphisms of IL-10 (-1082) and RANKL (-438) genes and the failure of dental implants. Int J Dent. 2017;2017.
• 67. Farooq M, Khan AW, Kim MS, Choi S. The Role of Fibroblast Growth Factor (FGF) Signaling in Tissue Repair and Regeneration. Cells. 2021;10(11):3242.
• 68. Katoh M. Fibroblast growth factor receptors as treatment targets in clinical oncology. Nat Rev Clin Oncol. 2019;16:105–122.
• 69. Akashi S, Ogata H, Kirikae F, et al. Regulatory roles for CD14 and phosphatidylinositol in the signaling via toll-like receptor 4-MD-2. Biochem Biophys Res Commun. 2000;268(1):172-177.
• 70. Li J, Qiao X, Shang J. Association analysis between CD14 gene polymorphisms and peri-implantitis susceptibility in a Chinese population. Immun Inflamm Dis. 2024;12(4).
• 71. Rakic M, Petkovic-Curcin A, Struillou X, et al. CD14 and TNFα single nucleotide polymorphisms are candidates for genetic biomarkers of peri-implantitis. Clin Oral Investig. 2015;19(4):791–801.
• 72. Qi Y, Li C, Du Y, et al. Chemokine Receptor 2 (CXCR2) Gene Polymorphisms and Their Association with the Risk of Developing Peri-Implantitis in Chinese Han Population. J Inflamm Res. 2021;14:1625–1631.
• 73. Saremi L, Esmaeilzadeh E, Ghorashi T, et al. Association of Fc gamma-receptor genes polymorphisms with chronic periodontitis and Peri-Implantitis. J Cell Biochem. 2019;120(7):12010-12017.
• 74. van Schie RC, Wilson ME. Evaluation of human FcgammaRIIA (CD32) and FcgammaRIIIB (CD16) polymorphisms in Caucasians and African-Americans using salivary DNA. Clin Diagn Lab Immunol. 2000;7(4):676-681.
• 75. Hans VM, Mehta DS. Genetic polymorphism of Fcγ-receptors IIa, IIIa, and IIIb in South Indian patients with generalized aggressive periodontitis. J Oral Sci. 2011;53(4):467-474.
• 76. Turkmen M, Firatli E. The study of genetic predisposition on periodontitis and peri-implantitis. Niger J Clin Pract. 2022;25(11):1799-1804.
• 77. Li P, Chen B, Zhao L, et al. Correlations of FCGR2A 131R/H and FCGR3A 158V/F Polymorphisms with the Susceptibility of Peri-implantitis in Chinese Han Population. Mol Biotechnol. 2024;66(9):2677.